Supercurrent in a Double Quantum Dot.

We demonstrate the Josephson effect in a serial double quantum dot defined in a nanowire with epitaxial superconducting leads. The supercurrent stability diagram adopts a honeycomb pattern. We observe sharp discontinuities in the magnitude of the critical current, I_{c}, as a function of dot occupation, related to doublet to singlet ground state transitions. Detuning of the energy levels offers a tuning knob for I_{c}, which attains a maximum at zero detuning. The consistency between experiment and theory indicates that our device is a faithful realization of the two-impurity Anderson model.

Joule spectroscopy of hybrid superconductor-semiconductor nanodevices.

Hybrid superconductor-semiconductor devices offer highly tunable platforms, potentially suitable for quantum technology applications, that have been intensively studied in the past decade. Here we establish that measurements of the superconductor-to-normal transition originating from Joule heating provide a powerful spectroscopical tool to characterize such hybrid devices. Concretely, we apply this technique to junctions in full-shell Al-InAs nanowires in the Little-Parks regime and obtain detailed information of each lead independently and in a single measurement, including differences in the superconducting coherence lengths of the leads, inhomogeneous covering of the epitaxial shell, and the inverse superconducting proximity effect; all-in-all constituting a unique fingerprint of each device with applications in the interpretation of low-bias data, the optimization of device geometries, and the uncovering of disorder in these systems. Besides the practical uses, our work also underscores the importance of heating in hybrid devices, an effect that is often overlooked.

Yu-Shiba-Rusinov screening of spins in double quantum dots.

A magnetic impurity coupled to a superconductor gives rise to a Yu-Shiba-Rusinov (YSR) state inside the superconducting energy gap. With increasing exchange coupling the excitation energy of this state eventually crosses zero and the system switches to a YSR ground state with bound quasiparticles screening the impurity spin by h/2. Here we explore indium arsenide (InAs) nanowire double quantum dots tunnel coupled to a superconductor and demonstrate YSR screening of spin-1/2 and spin-1 states. Gating the double dot through nine different charge states, we show that the honeycomb pattern of zero-bias conductance peaks, archetypal of double dots coupled to normal leads, is replaced by lines of zero-energy YSR states. These enclose regions of YSR-screened dot spins displaying distinctive spectral features, and their characteristic shape and topology change markedly with tunnel coupling strengths. We find excellent agreement with a simple zero-bandwidth approximation, and with numerical renormalization group calculations for the two-orbital Anderson model.

Evidence that treatment of ESRD patients with recombinant human erythropoietin induces immunosuppression without affecting the distribution of peripheral blood mononuclear cell subpopulations.

Fifteen patients with end-stage renal disease (ESRD) were blood sampled before and 1-, 2-, 3-, and 6 months after institution of recombinant human erythropoietin (r-HuEPO) therapy. Subpopulations of immunocompetent peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry using monoclonal antibodies against various T-lymphocyte antigens, B-lymphocytes, natural killer (NK)-cells, monocytes, and macrophages, and finally bone marrow progenitor cells. Functional properties of peripheral T-lymphocytes were analyzed by proliferation assays with mitogens, alloantigens and microbiological antigens. All patients but 3 responded with sufficient correction of the anaemia. The absolute number of leucocytes and lymphocytes remained unchanged during the study. Likewise, a remarkable intraindividual months to month constancy in the relative distribution of all PBMC subsets analyzed was recorded during the observation period, although some interindividual variability was observed. In contrast, the T-lymphocyte responsiveness decreased significantly except for 2 out of 11. We conclude, that treatment of renal anemia with r-HuEPO seems to induce immunosuppression in ESRD patients without affecting the distribution of various PBMC subsets.

Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly.

OBJECTIVE: The purpose of the present study was to compare the dosage requirements of recombinant human erythropoletin (rHuEPO) administered subcutaneously (SC) either one or three times weekly. DESIGN: A randomized, prospective study. SETTING: The patients were recruited from two university hospitals and five county hospitals. PATIENTS: Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal failure completed the study. INTERVENTIONS: Initially, all were treated with rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B). MAIN OUTCOME MEASURES: The Hb levels and rHuEPO doses at the start and at the end of the three-month study period. RESULTS: In group A the median Hb at randomization was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and 114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95) U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to 77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks. CONCLUSIONS: Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen.

[Peroral drug administration to children--are there any problems?]. / Peroral medicinsk behandling af børn--er der problemer?

Children's compliance with orally administered medicine is described. Five hundred questionnaires were given to the parents of children at their first visit at the out-patient clinic with a response from 484. Three hundred and ninety-seven children had been treated with oral medication in the form of liquid formulation or tablets, 257 within the previous year. Of these, 43.2% reported difficulties in taking the medication. Only 8.5% of the treatments had been interrupted. The main cause of the problems were the medications' taste and difficulties with swallowing tablets. The problems were more pronounced among the younger children. The administration of tablets was more difficult than the administration of liquids. There was no relationship between the problems and frequency of dosing, duration of treatment, severity of illness, social status of the parents, or the parents' age. In conclusion, prescription of better tasting mixtures and chewable tablets may reduce the problems associated with administering oral medication to children.

Absorption characteristics of once-a-day slow-release theophylline preparation in children with asthma.

The single- and multiple-dose absorption characteristics of a new sustained-release theophylline preparation, which has been formulated for once per day dosing in adults, were investigated in children aged 8 to 14 years. Four single doses were studied, each dose separated by 1 week. During steady state the preparation was given once daily in the morning for 1 week, and serum theophylline concentration was determined through two dosing intervals (48 hours). The product showed excellent sustained-release characteristics and consistent absorption profiles, which were not affected to any clinically important extent by the intake of various meals. After single doses, only 77% to 91% of the product was absorbed during the first 28 hours after dosing. However, bioavailability was complete both after single doses and during steady state. Eight of 14 children had steady-state fluctuations in serum theophylline levels of less than 90% when given doses once daily. Steady-state day-to-day variations in serum theophylline profiles were small in all patients except one, in whom differences up to 33 mumol/L (6 micrograms/mL) were seen (8 hours after dosing). We conclude that this formulation is completely absorbed at a sufficiently slow and consistent rate to permit acceptable fluctuations in absorption with once daily dosing for many, but not all, patients. However, it should not be used in very young children until bioavailability has been studied in this age group.

Fenoterol powder inhaler technique in children: influence of inspiratory flow rate and breath-holding.

The bronchodilator response after three different modes of inhalation of 0.2 mg fenoterol from a fenoterol powder inhaler was assessed in ten asthmatic children in a double-blind, placebo-controlled, cross-over study. There was a small, but statistically significant increase in response when the children inhaled as fast as possible, compared with very slow inhalations (16-19 l/min), but a breath-holding pause of 10 s after the inhalation had no significant effect on bronchodilation. Peak inspiratory flow through the inhaler, measured in 150 normal children aged 3.5-15 years, showed that all the children studied were able to generate a sufficient inspiratory flow to benefit from treatment with this inhaler. It is concluded that children using a fenoterol powder inhaler should be taught to inhale as fast as possible. They need not hold their breath after the inhalation.

Simplification of inhalation therapy in asthmatic children. A comparison of two regimes.

In a placebo-controlled double blind cross-over study of 3 X 3 weeks' duration the effectiveness of a new set of simple instructions for the use of spacer aerosols was compared with that of the rather complicated manufacturer's instructions in the daily treatment of 22 children with severe asthma. All children received inhaled budesonide and terbutaline at the lowest dose possible for satisfactory symptom control. Both the simple and complicated regimes were significantly better than placebo (P less than 0.01), but there was no indication that the complicated regime was superior to the simple regime. On the contrary, the children used significantly more rescue terbutaline and experienced more daytime symptoms when treated according to the complicated regime (P less than 0.01). 19 of 21 children who completed the study preferred to use the simple regime (P less than 0.01). It is concluded that instructions for the use of spacer aerosols should be substantially simplified and that conclusions from laboratory studies should be tested in the day-to-day management of asthmatics before these aerosols become widely used.

Food induced changes in theophylline absorption from a once-a-day theophylline product.

Bioavailability and the absorption pattern of theophylline from the sustained release theophylline (SRT) product, Uniphyllin, were studied in eight adults and eight children under fasting conditions in the morning, after a standardised breakfast in the morning, and under fasting conditions in the evening (adults only). Theophylline given intravenously was used as a reference. The extent of absorption of theophylline was complete for all administrations of SRT both in adults and children. In adults the absorption profiles after the three administrations of SRT were very similar and at no time point was there any difference in serum theophylline concentration or fraction absorbed between the three regimens. In addition, inter and intra individual variations in absorption were small. In children food caused a substantial change in the absorption pattern of theophylline so that the profiles became rather unpredictable with delays in absorption and periods of rapidly increasing serum drug concentrations. In three of the patients the dose dumping phenomenon resulted in toxic serum drug concentrations. Dumping of the dose could take place at any time interval between 3 and 15 h post dosing. Cmax was about 50% higher after fed than after fasting medication (P less than 0.01). It is concluded that children should not take SRT in large doses in combination with food.

Food and fasting absorption of a single dose of a sustained release theophylline sprinkle formulation in children.

The bioavailability and absorption pattern of theophylline from a single dose of a slow release theophylline sprinkle product (Somophyllin) were investigated in 10 asthmatic children both in fasting conditions and after a standardized breakfast. Theophylline given intravenously was used as a reference. The fasting absorption of Somophyllin was rather fast with peak serum theophylline levels 3-5 h (mean 3.7 h) after dosing. Food produced a small but statistically significant reduction in the rate of absorption of theophylline, so that the mean time to peak serum theophylline level was 5.6 h (range 4-8 h) after food. In no case was there any important difference between the absorption profiles on the test days, and the bioavailability was complete after both fasted and fed intake of the product (92.5% and 105%, respectively). It is suggested that to obtain the optimum absorption profile children should take Somophyllin with food rather than between meals.

Nephrotic syndrome in the first three months of life.

When the nephrotic syndrome develops within the first 3 months of life it is considered as congenital. In a review, different types of renal diseases are found behind the syndrome in early infancy. A classification of these is proposed, based on clinicopathology. Five classes with subgroups are described, and the necessity of recognizing these for prognosis, therapy and genetic counselling is emphasized.

Does erythropoietin cause hormonal changes in haemodialysis patients?

In 10 female and 10 male haemodialysis patients plasma FSH, LH, testosterone, prolactin, and somatotropin (STH) were estimated during erythropoietin (rHuEpo) treatment for 6 months. All but one patient responded with an increase in haemoglobin. The patients experienced improved sexual function according to the answers given in a self-administered questionnaire. Of the 90% who answered before the study 22% could not perform sexual activities whether they wanted to or not. During and at the end of the study 80 and 60% respectively answered, and none had these problems. In contrast, serum values of the sexual hormones (FSH, LH, testosterone and prolactin) were not significantly changed during rHuEpo therapy, and neither was the basal plasma STH.

Congenital nephrotic syndrome associated with Lowe's syndrome.

Two cases of the oculo-cerebro-renal syndrome of Lowe are reported, in which the course of the disease was very fast and unusual. Within the first hours after birth the patients developed nephrotic syndrome and died at the age of 45 and 4 days, respectively. Renal tissue obtained by biopsy and at autopsy disclosed pronounced glomerular changes.

Renal medullary cystic disease. Findings at urography and ultrasonography.

Medullary cystic disease (MCD) is an uncommon renal disease with adult onset and autosomal inheritance, eventually progressing to terminal renal failure. It may be difficult to identify because of insufficient diagnostic tools. At urography, the same ring-shaped accumulation of contrast medium at the corticomedullary junction was observed in two patients (mother and son) suffering from MCD. To our knowledge this observation has not been reported before.